[523] Cribriform-Morular Variant of Thyroid Carcinoma: Distinct Immunohistochemical Profile from Other Papillary Thyroid Carcinoma Variants

SB Lovitch, W Faquin, V Nose. Brigham and Women's Hospital, Boston, MA; Massachusetts General Hospital, Boston, MA

Background: Papillary thyroid carcinoma (PTC), the most common thyroid tumor, is typically well-differentiated and expresses HBME-1 and galectin-3; in contrast, poorly differentiated and anaplastic thyroid tumors are characterized by expression of p53 and Bcl-2 and high MIB-1 proliferative index. The cribriform-morular variant of thyroid carcinoma (CMv-TC) typically occurs as an extraintestinal manifestation of familial adenomatous polyposis (FAP), although rare sporadic cases have been reported. It occurs almost exclusively in young females, is well-differentiated, often multifocal, is characterized by cribriform, solid, and morular areas lacking typical nuclear features of papillary thyroid carcinoma, and is associated with germline and somatic mutations in the APC or beta catenin genes. In contrast to conventional PTC, CMv-TC rarely metastasizes and carries a benign prognosis.
Design: We reviewed nine cases of CMv-TC from our two institutions, and performed immunohistochemical analysis on a total of fourteen lesions from six cases. Clinical history and genetic test results were obtained from the medical record.
Results: All patients with CMv-TC were female and ranged in age from 18 to 51. All CMv-TC tumors showed strong nuclear and cytoplasmic accumulation of beta-catenin, expressed CK19, p53 and Bcl-2, and showed weak or absent expression of HBME-1 and galectin-3 (Table 1). MIB-1 index, and expression of S100 and 34BE12, were variable and did not distinguish CMv-TC from conventional PTC.

Table 1. APC Mutation and Immunohistochemical Profile of CMv-TC

Age/Sex	APC mutation	CK19	HBME-1	Galectin-3	-catenin (nuclear)	p53	Bcl-2
24/F	NK	++	+/-	+	+++	++	+++
24/F	+PTT seg. 2	++	-	+/-	+++	++	+++
18/F	R302X	++	-	-	+++	++	+++
51/F	R564X	++	-	-	+++	++	+++
49/F	+PTT seg. 2	++	-	+	+++	++	+++
18/F	D1948X	++	+/-	+	+++	++	++

NK, not known; PTT, protein truncation test.


Conclusions: CMv-TC is characterized by nuclear and cytoplasmic accumulation of beta catenin, immunoreactivity for CK19, p53 and Bcl-2, and lack of immunoreactivity for HBME-1 and galectin-3; these features are distinct from PTC, including classical, tall cell, and diffuse sclerosing variants. Expression of Bcl-2 and p53 in a well-differentiated tumor is unexpected, as these markers indicate dedifferentiation in PTC. Our findings suggest that CMv-TC should be classified as a distinct category of thyroid carcinoma arising in a familial setting, rather than as a variant of PTC.
Category: Endocrine

Monday, March 9, 2009 9:30 AM

Poster Session I Stowell-Orbison/Autopsy Award # 87, Monday Morning